In utero exposure to cigarette smoke and effects across generations: A conference of animals on asthma

Abstract

Summary Background The prevalence of asthma and chronic obstructive pulmonary disease (COPD) has risen markedly over the last decades and is reaching epidemic proportions. However, underlying molecular mechanisms are not fully understood, hampering the urgently needed development of approaches to prevent these diseases. It is well established from epidemiological studies that prenatal exposure to cigarette smoke is one of the main risk factors for aberrant lung function development or reduced fetal growth, but also for the development of asthma and possibly COPD later in life. Of note, recent evidence suggests that the disease risk can be transferred across generations, that is, from grandparents to their grandchildren. While initial studies in mouse models on in utero smoke exposure have provided important mechanistic insights, there are still knowledge gaps that need to be filled. Objective Thus, in this review, we summarize current knowledge on this topic derived from mouse models, while also introducing two other relevant animal models: the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. Methods This review is based on an intensive review of PubMed‐listed transgenerational animal studies from 1902 to 2018 and focuses in detail on selected literature due to space limitations. Results This review gives a comprehensive overview of mechanistic insights obtained in studies with the three species, while highlighting the remaining knowledge gaps. We will further discuss potential (dis)advantages of all three animal models. Conclusion/Clinical Relevance Many studies have already addressed transgenerational inheritance of disease risk in mouse, zebrafish or fly models. We here propose a novel strategy for how these three model organisms can be synergistically combined to achieve a more detailed understanding of in utero cigarette smoke‐induced transgenerational inheritance of disease risk.

Maternal preconception occupational exposure to cleaning products and disinfectants and offspring asthma

“…26 Emerging evidence from animal and human studies supports that environmental and occupational exposures might cause epigenetic changes that might be transmissible to offspring. [14][15][16][17][18][19][20][21][22]39 Such environmentally induced epigenetic alterations must be present in the germline to be transmissible to the next generation. 13,24 Alterations passed through the germline might result in inherited changes in gene expression in offspring in any kind of tissue and hence induce alteration in various tissues and cell types with impact on offspring phenotype.…”

“…13 Emerging evidence from human and animal models suggests that preconception parental exposures may influence the health of future generations. [14][15][16][17][18][19][20][21][22][23][24] Previous studies on maternal occupational exposure and respiratory health in offspring are scarce. [25][26][27] However, a registry study found that several parental occupations were associated with increased hospitalization for childhood asthma among offspring.…”

Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach

“…Lifestyle and environmental exposures are important risk factors for these diseases [ 3 , 4 ], not least when exposure occurs in early life. Emerging evidence suggests that the environment before conception may impair respiratory health of the offspring [ 5 , 6 ], as supported by animal research [ 7 – 9 ]. In line with this hypothesis, we previously found negative associations between fathers’ smoking before 15 years of age (a period compatible with prepuberty, as 15 years is the mean age of completed puberty in boys [ 10 ]) and their offspring's asthma phenotypes [ 11 , 12 ].…”

Perinatal exposure to nicotine alters spermatozoal DNA methylation near genes controlling nicotine action

“…Given the logistic limitations to study any human cohort across generations, particularly from a mechanistic perspective, animal models are used instead. Several animal models have been employed to study the effects of smoke exposure on developing lungs 1,3,12‐14 15 compelling evidence supports that most effects of perinatal smoke exposure on the developing lung, including the intergenerational and transgenerational transmission of the asthmatic phenotype, are caused by nicotine 6,7,16 .…”